Synergistic Deleterious Effect of High Fat Diet and World Trade Center Particulate Matter Exposure: An Assessment of Cardiopulmonary Dysfunction and Injury

Details

• Personal Author:
  Aristizabal O ; Caraher EJ ; Crowley G ; Kwon S ; Nolan A ; Oskuei A ; Ostrofsky D ; Veerappan A ; Wadghiri YZ
• Description:
  RATIONALE Metabolic syndrome(MetSyn),cardiovascular risk factors, and particulate matter (PM) exposure are increasingly prevalent global causes of airway hyperreactivity(AHR) and cardiopulmonary disease. MetSyn, LPA (oxidized LDL byproduct), serum vascular injury biomarkers, and an elevated pulmonary artery/aorta ratio are associated with the development of World Trade Center (WTC)-associated lung disease. Pulmonary and cardiovascular remodeling due to MetSyn and WTC-PM exposure are not well understood and are the focus of our work. While there are many ways of inducing metabolic syndrome in a murine model, we have chosen a HFD since it can increase weight and induce dyslipidemia in a mouse. METHODS: C57Bl/6 wild type (WT) mice (n=8/group), aged 6-8 weeks were fed HFO (60% of calories from lard; 012492i; Research Diets) or normal diet (ND) with 13% of calories from fat. After 12-weeks of HFD and ≥20% weight gain when compared to age matched NO controls, oropharyngeal aspiration of 200ug WTC-PM53 or an equal volume of PBS was administered. 24-h after exposure, all mice underwent noninvasive cardiac echocardiography(Vevo-3100) and pulmonary mechanics assessment(Flexivent). Plasma was measured for LPA(Echelon). Comparisons made by student's t-test. lmmunohistochemistry for alpha-smooth muscle actin (a-SMA(Santa Cruz)) was performed on cardiac/lung tissue. RESULTS Mice fed a HFD had mean 22.3% higher body weight than ND, Fig. 1A. 24hrs after exposure, LPA fold-change was significantly increased in HFD,PM mice compared to ND-PM or HFD,PBS mice, Fig. 1 B. HFD-PM and ND-PM mice had significantly lower FEV0.1 compared to PBS ctrls of either diet, Fig. 1C . PC200 the provocative concentration of methacholine (Mch) required to double resistance from baseline. was calculated for each mouse by interpolation. Fig. 1C. HFD and WTC-PM co-exposure decreased PC200 in a synergistic manner compared to ND-PM and HFD-PBS, Fig.1 E. HFD mice when exposed to PM showed a significant decrease in ejection traction(EF) when compared to PBS, Fig. 1 F. Further, a-SMA was highly expressed in HFD-PM exposed mice compared to HFD-PBS. Fig. 1G.J. CONCLUSIONS HFD-PM coexposure can induce AHR in a murine model similar to what is seen in the WTC-exposed firefighter cohort. LPA, a potential pathway that links MetSyn and pulmonary disease, is increased in HFD-PM co-exposure. Echocardiography results indicate that PM exposure in obesity causes subsequent cardiopulmonary dysfunction. Further studies will include collagen, metabolite and echocardiographic assessment at both acute and chronic timepoints. [Description provided by NIOSH]
• Subjects:
  Animals Cohort Studies Diet Firefighters Lung Occupational Health Particulate Matter Respiratory System Safety September 11 Terrorist Attacks
• Keywords:
  Animal Studies Cohort Studies Dietary Effects Fire Fighters Lung Function Nutrition Particulates World Trade Center WTC
• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Abstract or Summary
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  201
• NIOSHTIC Number:
  nn:20066337
• Citation:
  Am J Respir Crit Care Med 2020 May; 201(Abstract Issue):A1790
• Email:
  arul.veerappan@nyulangone.org
• Federal Fiscal Year:
  2020
• Performing Organization:
  New York University School of Medicine
• Peer Reviewed:
  False
• Start Date:
  20170701
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Abstract Issue
• End Date:
  20260630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:11d7382a5184301fe5587279bbab48a9a4d0b00b4ee749364263cdb965b46c520a41ced7bb0beca6274cbb8cd6cad90212c4fc82b819663e10e9cbe3d730cf2d
• Download URL:
  https://stacks.cdc.gov/view/cdc/212806/cdc_212806_DS1.pdf
• File Type:
  [PDF - 260.44 KB ]